Cannabinoids, cannabis, and cannabis-based medicines for pain management: an overview of systematic reviews

Cannabinoids, cannabis, and cannabis-based medicines (CBM) are increasingly used to manage pain, with limited understanding of their efficacy and safety. We assessed methodological quality, scope, and results of systematic reviews of randomised controlled trials of these treatments. Several search strategies sought self-declared systematic reviews. Methodological quality was assessed using both AMSTAR-2 and techniques important for bias reduction in pain studies. Of the 106 articles read, 57 were self-declared systematic reviews, most published since 2010. They included any type of cannabinoid, cannabis, or CBM, at any dose, however administered, in a broad range of pain conditions. No review examined the effects of a particular cannabinoid, at a particular dose, using a particular route of administration, for a particular pain condition, reporting a particular analgesic outcome. Confidence in the results in the systematic reviews using AMSTAR-2 definitions was critically low (41), low (8), moderate (6), or high (2). Few used criteria important for bias reduction in pain. Cochrane reviews typically provided higher confidence; all industry-conflicted reviews provided critically low confidence. Meta-analyses typically pooled widely disparate studies, and, where assessable, were subject to potential publication bias. Systematic reviews with positive or negative recommendation for use of cannabinoids, cannabis, or CBM in pain typically rated critically low or low (24/25 [96%] positive; 10/12 [83%] negative). Current reviews are mostly lacking in quality and cannot provide a basis for decision-making. A new high-quality systematic review of randomised controlled trials is needed to critically assess the clinical evidence for cannabinoids, cannabis, or CBM in pain

Cannabinoids, cannabis and cannabis-based medicine for pain management: a systematic review of randomised controlled trials

ABSTRACT: Cannabinoids, cannabis, and cannabis-based medicines (CBMs) are increasingly used to manage pain, with limited understanding of their efficacy and safety. We summarised efficacy and adverse events (AEs) of these types of drugs for treating pain using randomised controlled trials: in people of any age, with any type of pain, and for any treatment duration. Primary outcomes were 30% and 50% reduction in pain intensity, and AEs. We assessed risk of bias of included studies, and the overall quality of evidence using GRADE. Studies of &lt;7 and &gt;7 days treatment duration were analysed separately. We included 36 studies (7217 participants) delivering cannabinoids (8 studies), cannabis (6 studies), and CBM (22 studies); all had high and/or uncertain risk of bias. Evidence of benefit was found for cannabis &lt;7 days (risk difference 0.33, 95% confidence interval 0.20-0.46; 2 trials, 231 patients, very low-quality evidence) and nabiximols &gt;7 days (risk difference 0.06, 95% confidence interval 0.01-0.12; 6 trials, 1484 patients, very low-quality evidence). No other beneficial effects were found for other types of cannabinoids, cannabis, or CBM in our primary analyses; 81% of subgroup analyses were negative. Cannabis, nabiximols, and delta-9-tetrahydrocannabinol had more AEs than control. Studies in this field have unclear or high risk of bias, and outcomes had GRADE rating of low- or very low-quality evidence. We have little confidence in the estimates of effect. The evidence neither supports nor refutes claims of efficacy and safety for cannabinoids, cannabis, or CBM in the management of pain.</p

Signature for Pain Recovery IN Teens (SPRINT): protocol for a multisite prospective signature study in chronic musculoskeletal pain

INTRODUCTION: Current treatments for chronic musculoskeletal (MSK) pain are suboptimal. Discovery of robust prognostic markers separating patients who recover from patients with persistent pain and disability is critical for developing patient-specific treatment strategies and conceiving novel approaches that benefit all patients. Given that chronic pain is a biopsychosocial process, this study aims to discover and validate a robust prognostic signature that measures across multiple dimensions in the same adolescent patient cohort with a computational analysis pipeline. This will facilitate risk stratification in adolescent patients with chronic MSK pain and more resourceful allocation of patients to costly and potentially burdensome multidisciplinary pain treatment approaches. METHODS AND ANALYSIS: Here we describe a multi-institutional effort to collect, curate and analyse a high dimensional data set including epidemiological, psychometric, quantitative sensory, brain imaging and biological information collected over the course of 12 months. The aim of this effort is to derive a multivariate model with strong prognostic power regarding the clinical course of adolescent MSK pain and function. ETHICS AND DISSEMINATION: The study complies with the National Institutes of Health policy on the use of a single internal review board (sIRB) for multisite research, with Cincinnati Children's Hospital Medical Center Review Board as the reviewing IRB. Stanford's IRB is a relying IRB within the sIRB. As foreign institutions, the University of Toronto and The Hospital for Sick Children (SickKids) are overseen by their respective ethics boards. All participants provide signed informed consent. We are committed to open-access publication, so that patients, clinicians and scientists have access to the study data and the signature(s) derived. After findings are published, we will upload a limited data set for sharing with other investigators on applicable repositories. TRIAL REGISTRATION NUMBER: NCT04285112

I am great, but only when I also want to dominate: Maladaptive narcissism moderates the relationship between adaptive narcissism and performance under pressure

Narcissism-performance research has focused on grandiose narcissism but has not examined the interaction between its so-called adaptive (reflecting over-confidence) and maladaptive (reflecting a domineering orientation) components. In this research, we tested interactions between adaptive and maladaptive narcissism using two motor tasks (basketball and golf in Experiments 1-2, respectively) and a cognitive task (letter transformation; Experiment 3). Across all experiments, adaptive narcissism predicted performance under pressure only when maladaptive narcissism was high. In the presence of maladaptive narcissism, adaptive narcissism also predicted decreased pre-putt time in Experiment 2 and an adaptive psychophysiological response in Experiment 3, reflecting better processing efficiency. Findings suggest that individuals high in both aspects of narcissism perform better under pressure thanks to superior task processing. In performance contexts, the terms “adaptive” and “maladaptive” – adopted from social psychology – are over-simplistic and inaccurate. We believe that self-inflated narcissism and dominant narcissism are better monikers for these constructs.N/

Mechanisms of urethral continence and their clinical application

Controversy about the basic nature of urethral function does not preclude accurate clinical assessment of disorders of function. While the precise method of treatment of urethral continence dysfunction varies from institution to institution, the basic techniques are quite similar. It is the application of a treatment method to a particular case which causes difficulty. It is important, therefore, to have some understanding of the functional elements in the urethral continence mechanism to be able to determine which element does not function. Most cases of intractable incontinence are associated with poor function of the involuntary part of the sphincter. In general, peak urethral closing pressures are unrelated to continence function unless there is no pressure at all.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47059/1/345_2004_Article_BF00326702.pd

Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is the most common acute hyperglycaemic emergency in people with diabetes mellitus. A diagnosis of DKA is confirmed when all of the three criteria are present — ‘D’, either elevated blood glucose levels or a family history of diabetes mellitus; ‘K’, the presence of high urinary or blood ketoacids; and ‘A’, a high anion gap metabolic acidosis. Early diagnosis and management are paramount to improve patient outcomes. The mainstays of treatment include restoration of circulating volume, insulin therapy, electrolyte replacement and treatment of any underlying precipitating event. Without optimal treatment, DKA remains a condition with appreciable, although largely preventable, morbidity and mortality. In this Primer, we discuss the epidemiology, pathogenesis, risk factors and diagnosis of DKA and provide practical recommendations for the management of DKA in adults and children

Mitochondrial Disease and Anesthesia

It is increasingly common for children with mitochondrial disease to undergo surgery and anesthesia. Although many different anesthetics have been used successfully for these patients, serious, unexpected complications have occurred during and following anesthetic exposure. This has led to the widespread opinion among anesthesiologists that mitochondrial patients are at increased risk from the stress of surgery and anesthesia. Defects in function of the mitochondrial electron transport chain can lead to striking hypersensitivity to volatile anesthetics in children. Despite this striking finding, the connection between mitochondrial function and response to anesthetics is unknown. We review here the anesthetic considerations for patients with mitochondrial defects. In addition, we present an approach to anesthetic care of these patients at our institutions